The invention relates to biologically active peptides and polypeptides and methods for administering them orally. Advances in the fields of genetic engineering, biotechnology, and peptide chemistry have led to the development of ever increasing number of proteins and peptides that have potential utility as pharmaceutical agents. The development of methods for administering these new pharmaceutical agents is thus of ever increasing importance. In particular, the local or systemic administration of biologically active substances, such as peptides and proteins, is a current concern.
The delivery of peptides and proteins can be complicated, as peptides and proteins are subject to degradation in many physiological environments. For example, while oral delivery is often desirable, it exposes polypeptides to harsh conditions. Enteric coated compositions are useful in overcoming the degradation of peptides and proteins in the stomach due to acidic conditions. Enteric coating materials are generally anionic polymers that are insoluble in buffer solutions below about pH 5 and in gastric fluid but soluble in neutral to weakly alkaline buffer solutions above about pH 5.5 and in intestinal fluid. Release of the medicament within the enteric coating may occur by dissolution, leaching, erosion, rupture, diffusion, or similar actions, depending upon such factors as the nature and thickness of the coating material. Alternatively, some polypeptides are naturally resistant to acidic conditions, and can be delivered to the intestines in the absence of such coatings.
However, once reaching the intestines, certain peptides and polypeptides may be susceptible to proteolytic digestion by enzymes such as trypsin and chymotrypsin, thereby limiting the bioavailability and half-life of the drug.
Improved formulations and methods of delivery that enhance the stability of therapeutic polypeptides in the intestines are of interest for clinical purposes. The present invention addresses this need.